Strategies for overcoming multiple barriers of oral administration of protein and peptide therapeutics

Jan 26, 2026Materials today. Bio

Ways to improve oral delivery of protein and peptide medicines by overcoming multiple barriers

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Abstract

This review discusses strategies to enhance the bioavailability of protein and peptide therapeutics (PPs) in the complex gastrointestinal environment.

  • Four main gastrointestinal barriers to oral PPs are identified: harsh pH, enzymatic degradation, the mucus layer, and the intestinal epithelial barrier.
  • Chemical modifications, permeation enhancers, and encapsulation techniques are evaluated as potential solutions to improve the stability and absorption of PPs.
  • Novel delivery systems such as microneedles and nanoparticle-based carriers are explored for their ability to protect PPs during transit through the GI tract.
  • The advantages and limitations of each strategy are compared, highlighting the need for a synergistic approach to effectively address multiple GI barriers.
  • Current challenges in oral PPs drug delivery systems are discussed, along with future directions for improving therapeutic outcomes.

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